RFA-FD-14-080: Predictive in vitro Methods for Characterizing Product Performance, Case Study: Furosemide Project Summary / Abstract: The overall aim of the current grant application is to develop in vitro models that can predict drug performance in the pediatric patient. This will be achieved in an iterative process. First a throughout review of the gastro-intestinal physiology of the pediatric patient will be carried out. Then, based on this, a range of physiologically relevant media, simulating the pediatric gastric and intestinal fluids, will be composed. These will also include typically infant meals, such as milk, baby formula and Ensure Plus. The media will be used in modified compendial dissolution apparatuses, adjusted eg with regard to volume, to better simulate the pediatric patient. In addition, models closer simulating the gastro- intestinal physiology, eg the Dynamic Gastric Model will be employed. Data obtained will be compared to available in vivo data, and the models modified as to optimize the prediction of the in vivo performance. Finally, the data will be used in the development of physiologically based pharmacokinetic models. The project will therefore increase the current knowledge and understanding of the performance of poorly soluble drugs in the pediatric population and as such provide a basis for better formulations and thereby also an improved dosing regime for the better of the pediatric patient.